The present invention relates to novel collagen fibers for use in medical treatments and a process for preparing the same.
More in detail, the present invention relates to novel collagen fibers suitable for use in medical treatments prepared by dispersing refined collagen into an aqueous acidic solution and treating the thus obtained aqueous dispersion with a specified amount of energy by ultrasonic irradiation.
Collagen is a protein composed of corium, cartilage, bone, tendon, etc., and exists in the animal in a fibrilar or fiberlike state consisting of bound molecular collagens of about 2800 .ANG. in molecular length and of about 15 .ANG. in diameter which is called tropocollagen.
Since the cross-linking bonds generally proceeds between the molecules of collagen in the animal body with the aging of the animal, in the body of aged animal, the major part of collagen is "insoluble collagen".
The "insoluble collagen" in the present invention is collagen which is insoluble in an aqueous solution of an acid or a salt.
The collagen fibers obtained by mechanical fibrating or by chemical treatment of the insoluble collagen, having a property to be absorbed into the living body (bio-absorbability) and blood-coagulating property other than the low antigenic property have been expected as the blood-coagulant absorbable into the living body and the wound-treating material in the field of medical purpose.
The method of mechanical fibrating of collagen is a method in which insoluble collagen obtained from oxhide and the like is mechanically and severely crushed to be fibrated. However, even by such a mechanical means, the cross-linked bonds between the molecules of collagen are hardly broken, and accordingly, the collagen fibers obtained by mechanical fibrating are not excellent in bio-absorbability and in compatibility to living body.
In addition, since the quality of collagen fibers obtained by the mechanical means of fibrating depends largely on the kinds, the sex and the age of the animal from which collagen is derived, the collagen fibers having the uniform quality for use in medical treatments can not be always provided. For instance, the isoelectric point of insoluble collagen as the raw material of collagen fibers is the broad range of pH 5 to pH 8. The isoelectric point of insoluble collagen is one of the physical constants which indicate the degree of cross-linking between the molecules of collagen, and mainly depends on the kinds and the age of the animal. Accordingly, such a variation of the isoelectric point of insoluble collagen shows the difficulty of the production of the uniform quality of the insoluble collagen in the case where it is used for medical treatments.
As a method for solving the problem, the process for preparing "soluble collagen" fibers by selectively digesting and cutting the cross-linking bonds with protease without mechanically braking the molecules of collagen has been proposed (so-called the method for solubilizing by an enzyme).
The "soluble collagen" of the invention is collagen which may be soluble in an aqueous solution of an acid.
The method for solubilizing by an enzyme gives the collagen fibers having improved bio-absorbability and capability and the uniform quality, and then the method for solubilizing by an enzyme attain the initial object. However, the collagen fibers obtained by the method for solubilizing by an enzyme is not always satisfactory from the viewpoint of the poor blood-coagulating property of the product and of the high cost due to the use of expensive and unstable protease and the inability to re-use the protease.
In addition, according to the method for solubilizing by an enzyme, it is almost impossible to completely remove the protease intermixed into the soluble collagen fibers or to lose an activity of the enzyme without thermally denaturing the solubilized collagen fibers.
Accordingly, it is considered questionable from the viewpoint of safety to apply the soluble collagen fibers obtained by the method for solubilization by an enzyme to living bodies in the medical purpose. Further, it is difficult to control the action of the enzyme in digestion and cutting of the cross-linking bonds of raw collagen, and the attempts to obtain the homogeneity of the product inevitably lead to bring collagen into molecular state. The time period between the addition of collagen into a blood specimen and the beginning of blood-coagulation has a relationship to the degree of cross-linking between the molecules of collagen, and it is said that the time period is very long in the case of adding molecular collagen into the blood specimen.
Consequently, the conventional methods for obtaining the solubilized collagen fibers are not always satisfactory from the view-points of industry, economy and quality.
The object of the present invention is to provide collagen fibers having excellent in the properties such as bio-absorbability and velocity of blood-coagulation for use in medical treatments.
Another object of the present invention is to provide a process for producing collagen fibers for use in medical treatments. The other object of the present invention is to provide a hemostatica comprising collagen fibers for use in medical treatments.